GATA-3 seals Notch-induced T cell commitment (46.1)

Transcription factors orchestrate T-lineage differentiation in the thymus. One early checkpoint involves Notch-1 stimulation of thymic immigrants that promotes T-cell commitment at the expense of the B-lineage program. The zinc-finger transcription factor GATA-3 is required for T cell specification, although its mechanism of action is unknown. Here we identify molecular targets of GATA-3 in early thymocytes and show that conditional ablation of GATA-3 expression in committed pro-T-cells unmasks a latent B-cell potential that is undetectable in normal T-cell precursors. Thus, GATA-3 delimits the developmental options in early thymocyte precursors by sealing T-cell fate induced by Notch signals. M.E. García-Ojeda was funded by a Pasteur Foundation Fellowship. This work was supported by grants from the Institut Pasteur, the Inserm and the Ligue Nationale contre le Cancer. M.E. Garcia-Ojeda and F. Lemaître contributed equally to this work.